This proposal is to acquire funds for X-ray diffractometer for the structural biology laboratory at The Salk Institute. The 30 cm imaging plates (MacScience) with MacScience diffractometer have been the work force in constant use since 1994. After nearly 13 years, the system has become costly to maintain. Furthermore, the X-ray technology has advanced significantly. We have completed a test run on Rigaku's MicroMax 007 system and compared it to the data quality achievable with our MacScience system. The new system is at least 10 times efficient and it is critical for us to replace and upgrade the system as soon as we can. X-ray system has been powerful tool for research in many laboratories at the Salk Institute to develop and expand their frontier research through the understanding of the atomic structures of biological macromolecules. There are 11 PIs, including five main users, whose research activities require constant access to the diffractometer system. From 1994 to 2006, we at Salk have produced over 150 structure-related publications in leading journals including 10 in Nature, 7 in Science, 2 in Cell. These studies laid foundations for advancement in various areas and made seminal discoveries by completing the cycle of structure-function studies of membrane receptors, ligand- and DNA-binding proteins, metabolic and engineered enzymes, ion channels, and proteins involved in signal transduction. The research activities cover a wide range of questions. Structures of integral membrane proteins which constitute nearly 70% of therapeutic targets are of outmost importance (W. Kwiatkowski). Designing new therapeutics by engineering enzyme metabolic pathways gives a new prospect for medicine (J. Noel, L.Wang). The structures of betaglycan and cripto complexes are important in developing cancer therapeutics (W. Vale). Ion channels play a significant role in neurological diseases (S. Choe, P. Slesinger) as do enzymes involved in gene expression (S. Pfaff). Structures of amyloid-forming peptide are crucial to understand and treat Altzheimer's or Parkinson's disease (R. Riek) and finally structures of nuclear hormone receptors can be used to design activators for obesity treatment (R. Evans). Checkpoint protein kinase, Chk1 (T. Hunter), aminotransferase and brassinosteroid binding proteins (J. Chory) are studied to understand their signaling mechanisms. [unreadable] [unreadable] [unreadable]